5-Fluoro-1-(3-metylbutano­yl)pyrimidine-2,4(1H,3H)-dione

The 3-methyl­butanoyl group and the 5-fluoro­uracil unit of the title compound, C9H11FN2O3, are essentially coplanar, with the carbonyl group oriented towards the ring CH group and away from the nearer ring carbonyl group. The 3-methyl­butanoyl (C=)C—N—C=O torsion angle of 9.6 (2)° is comparable to that in structurally related compounds. In the solid state, two inversion-related mol­ecules form N—H⋯O hydrogen bonds to generate an inter­molecular R 2 2(8) ring. The crystal structure also diplays intra- and inter­molecular C—H⋯O inter­actions

5-Fluoro-1-(penta­noyl)pyrimidine-2,4(1H,3H)-dione

The penta­noyl group and the 5-fluoro­uracil moiety of the title compound, C9H11FN2O3, are essentially coplanar, with the penta­noyl carbonyl group oriented towards the ring CH group and away from the nearer ring carbonyl group. In the crystal structure, two inversion-related mol­ecules form a dimer structure, in which two N—H⋯O hydrogen bonds generate an inter­molecular R 2 2(8) ring. In addition, there are intra- and inter­molecular C—H⋯O inter­actions

2,2\u27,5\u27,6-Tetrachloro-4-[(1\u3cem\u3eS\u3c/em\u3e)-1-methylpropoxy]biphenyl

In the title molecule, C16H14Cl4O, the dihedral angle between the least-square planes of the benzene rings is 84.40 (7)°. No unusual intermolecular interactions are present

5,5\u27-Dichloro-2,2\u27-dimethoxybiphenyl

In the title molecule, C14H12Cl2O2, the dihedral angle between the least-square planes of the benzene rings is 62.17 (6)°. Both methoxy groups are slightly out of the plane of the benzene rings to which they are attached, making dihedral angles of 4.22 (18) and 18.82 (16)°

Absolute Configuration of 2,2\u27,3,3\u27,6-Pentachlorinatedbiphenyl (PCB 84) Atropisomers

Nineteen polychlorinated biphenyl (PCB) congeners, such as 2,2′,3,3′,6-pentachlorobiphenyl (PCB 84), display axial chirality because they form stable rotational isomers, or atropisomers, that are non-superimposable mirror images of each other. Although chiral PCBs undergo atropselective biotransformation and atropselectively alter biological processes, the absolute structure of only a few PCB atropisomers has been determined experimentally. To help close this knowledge gap, pure PCB 84 atropisomers were obtained by semi-preparative liquid chromatography with two serially connected Nucleodex β-PM columns. The absolute configuration of both atropisomers was determined by X-ray single-crystal diffraction. The PCB 84 atropisomer eluting first and second on the Nucleodex β-PM column correspond to (aR)-(−)-PCB 84 and (aS)-(+)-PCB 84, respectively. Enantioselective gas chromatographic analysis with the β-cyclodextrin-based CP-Chirasil-Dex CB gas chromatography column showed the same elution order as the Nucleodex β-PM column. Based on earlier reports, the atropisomers eluting first and second on the BGB-172 gas chromatography column are (aR)-(−)-PCB 84 and (aS)-(+)-PCB 84, respectively. An inversion of the elution order is observed on the Cyclosil-B gas chromatography and Cellulose-3 liquid chromatography columns. These results advance the interpretation of environmental and human biomonitoring as well as toxicological studies

Partitioning of perfluorooctanoate into phosphatidylcholine bilayers is chain length-independent

The chain length dependence of the interaction of PFOA, a persistent environmental contaminant, with dimyristoyl- (DMPC), dipalmitoyl- (DPPC) and distearoylphosphatidylcholine (DSPC) was investigated using steady-state fluorescence anisotropy spectroscopy, differential scanning calorimetry (DSC) and dynamic light scattering (DLS). PFOA caused a linear depression of the main phase transition temperature Tm while increasing the width of the phase transition of all three phosphatidylcholines. Although PFOA\u27s effect on Tm and the transition width decreased in the order DMPC \u3e DPPC \u3e DSPC, its relative effect on the phase behavior was largely independent of the phosphatidylcholine. PFOA caused swelling of DMPC but not DPPC and DSPC liposomes at 37 °C in the DLS experiments, which suggests that PFOA partitions more readily into bilayers in the fluid phase. These findings suggest that PFOA\u27s effect on the phase behavior of phosphatidylcholines depends on the cooperativity and state (i.e., gel versus liquid phase) of the membrane. DLS experiments are also consistent with partial liposome solubilization at PFOA/lipid molar ratios \u3e 1, which suggests the formation of mixed PFOA–lipid micelles

3,4\u27,5-Trichlorobiphenyl-4-yl 2,2,2-trichloroethyl sulfate

Crystals of the title compound, C14H8Cl6O4S, are twinned by inversion, with unequal components [0.85 (3):0.15 (3)]. The asymmetric unit contains two independent molecules that are related by a pseudo-inversion center. The Car-O [1.393 (9) and 1.397 (9) Å] and ester S-O bond lengths [1.600 (5) and 1.590 (5) Å] of both molecules are comparable to the structurally related 2,3,5,5-trichlorobiphenyl-4-yl 2,2,2-trichloroethyl sulfate. The dihedral angles between the benzene rings in the two molecules are 37.8 (2) and 35.0 (2)°

4′-Chloro­biphenyl-4-yl 2,2,2-trichloro­ethyl sulfate

The title compound, C14H10Cl4O4S, is an inter­mediate in the synthesis of the PCB sulfate monoester of 4′-chloro-biphenyl-4-ol. Both the sulfate monoester and 4′-chloro-biphenyl-4-ol are metabolites of PCB 3 (4-chloro­biphen­yl). There are two mol­ecules with different conformations in the asymmetric unit. The solid state dihedral angles between the benzene rings are 18.52 (10) and 41.84 (16)° in the two mol­ecules, whereas the dihedral angles between the least-squares plane of the sulfated benzene ring and O—S (Ar—C—O—S) are 66.2 (3) and 89.3 (3)°. The crystal was an inversion twin with a refined component fraction of 0.44 (7)

Evaluating the Role of the Steroid and Xenobiotic Receptor (SXR/PXR) in PCB-153 Metabolism and Protection against Associated Adverse Effects during Perinatal and Chronic Exposure in Mice.

BACKGROUND:Polychlorinated biphenyls (PCBs) are environmental toxicants; PCB exposure has been associated with adverse effects on wildlife and humans. However, the mechanisms underlying these adverse effects are not fully understood. The steroid and xenobiotic receptor [SXR; also known as the pregnane X receptor (PXR) and formally known as NR1I2] is a nuclear hormone receptor that regulates inducible metabolism of drugs and xenobiotics and is activated or inhibited by various PCB congeners. OBJECTIVES:The aim of this study was to investigate the effects of exposure to PCB-153, the most prevalent PCB congener in human tissues, on SXR knockout mice (SXRKO) and to elucidate the role of SXR in PCB-153 metabolism and promotion of its harmful effects. METHODS:Wild-type (WT) and SXRKO mice were chronically or perinatally exposed to a low dose (54μg/kg/d) of PCB-153. Blood, livers, and spleens were analyzed using transcriptome sequencing (RNA-seq) and molecular techniques to investigate the impacts of exposure on metabolism, oxidative stress, and hematological parameters. RESULTS:SXRKO mice perinatally exposed to PCB-153 displayed elevated oxidative stress, symptoms of hemolytic anemia, and premature death. Transcriptomal analysis revealed that expression of genes involved in metabolic processes was altered in SXRKO mice. Elevated levels of the PCB-153 metabolite, 3-OH-PCB-153, were found in exposed SXRKO mice compared to exposed WT mice. Blood hemoglobin (HGB) levels were lower throughout the lifespan, and the occurrence of intestinal tumors was larger in SXRKO mice chronically exposed to PCB-153 compared to vehicle and WT controls. DISCUSSION:Our results suggest that altered metabolism induced by SXR loss of function resulted in the accumulation of hydroxylated metabolites upon exposure to PCB-153, leading to oxidative stress, hemolytic anemia, and tumor development in a mouse model. These results support a major role for SXR/PXR in protection against xenobiotic-induced oxidative stress by maintaining proper metabolism in response to PCB-153 exposure. This role of SXR could be generally applicable to other environmental toxicants as well as pharmaceutical drugs. https://doi.org/10.1289/EHP6262